COVALENT INTERACTIONS OF ESTROGENS IN TARGET TISSUES

了解雌二醇代谢在卵巢癌生物学中的作用， 激素是必不可少的知道其不同的生物效应 代谢产物 这个项目是关于蜂窝 16 α-羟基雌酮和2-羟基雌酮的相互作用，主要 雌二醇代谢物，其生物学特性不同于 母体激素 16 α-羟基雌酮与 伯氨基通过席夫碱形成和随后的Heyns 重排 2-羟基雌酮与亲核试剂如 巯基也与生物分子形成共价键。 这两个过程已被证明进行细胞成分在体外 并且被认为在生理学上是重要的， 雌激素作用的病理生理学。 将寻求以下方面的准确信息： 雌激素靶向中这种共价键形成亚细胞位点 组织和特定生物大分子的性质 参与这些互动。 这些生物学后果 将在体外和体内研究中探索这些过程， 合适的实验模型。 预计这些研究将 揭示了这些天然雌激素在女性生殖相关疾病中的作用， 疾病

To understand the role of metabolism of estradiol in the biology of the hormone it is essential to know the biological effects of its diverse metabolic products. This project is concerned with the cellular interactions of 16Alpha-hydroxyestrone and 2-hydroxyestrone, major metabolites of estradiol with biological properties distinct from those of the parent hormone. 16Alpha-hydroxyestrone forms covalent linkages with primary amino groups via Schiff base formation and subsequent Heyns rearrangement. 2-Hydroxyestrone reacts avidly with nucleophiles such as sulfhydryl groups to also form covalent bonds with biological molecules. Both processes have been shown to proceed with cellular components in vitro and in vivo and are considered to be of importance in the physiology and pathophysiology of estrogen action. Precise information will be sought on the subcellular sites of such covalent bond formation in estrogen target tissues and on the nature of the specific biological macromolecules involved in these interactions. The biological consequence of these processes will be explored in in vitro and in vivo studies employing appropriate experimental models. It is expected that these studies will shed light on the role of these natural estrogens in hormonally linked diseases.